A highly diastereoselective approach to conformationally constrained serine analogues: Synthesis of an alpha-amino-beta-hydroxycyclohexenecarboxylic acid and derivatives

A diastereospecific synthesis of alpha-amino-beta-hydroxycyclohexenecarboxy lic acid (7) was found starting from 4-chloromethylene-5(4H)-oxazolone (1) which reacted with 2,3-dimethylbutadiene in the presence of EtAlCl2. The Di els-Alder reaction gave two diastereoisomeric cycloadducts 2 and 3, dependi ng on the configuration of the starting dienophile 1. Compounds 2a and 3 we re transformed into the ester 4 and the oxazoline 6, respectively, by react ion with MeOH and p-TSA. The reaction of 2a and 3 with dimethylamine in eth anol solution gave the corresponding amides 8 and 9, respectively, which we re transformed into the bicyclic oxazoline 10 on reaction with Na2CO3 in ac etonitrile. On acidic hydrolysis both oxazolines 6 and 10 were transformed into alpha-amino-beta-hydroxycyclohexenecarboxylic acid (7) that includes t he serine skeleton.